Description:
Reference #: 01259
The University of South Carolina is offering licensing opportunities for using therapies that mimic the regeneration of the zonal organization of articular cartilage.
Background:
Approximately 12% of all osteoarthritis (OA) cases are caused by post-traumatic osteoarthritis (PTOA). About 3.5 million individuals in US suffer from PTOA of the hip, knee, or ankle with a total cost of $3 billion to the health care system. PTOA can occur in any age from any acute physical trauma such as sports, vehicle accidents, falls, or military injury. PTOA results in some form of permanent disability in 28% of patients with traumatic skeletal injuries. The rapidly applied load in traumatic injuries focally disrupts the articular cartilage, beginning with cell death, inadequate synthesis of proteoglycans, and disturbed proteoglycan to water ratio, which leads to decreased stiffness and accelerated damage to the remainder of the joint. PTOA is diagnosed on average 19 months following traumatic injury such that the focal articular disruption has advanced to a full-thickness defect. Conventional clinical approaches to treatment of full-thickness chondral defects such as subchondral drilling, micro-fracture, and abrasion arthroplasty create mechanically inferior fibrocartilage. Osteochondral autograft transfer or mosaicplasty suffers from an additional surgical intervention and donor site morbidity. Autologous chondrocyte implantation (ACI) reduces fibrocartilage formation but it fails to restore zonal organization of the articular cartilage and in some cases leads to peripheral hypertrophy and calcification. For example, 33% of ACI procedures performed on patients suffering from PTOA of the knee resulted in permanent disability. Therefore, therapies that can regenerate the zonal organization of articular cartilage could prevent permanent disability in patients suffering from PTOA.
Invention Description:
The subject invention is a post-traumatic osteoarthritis (PTOA) therapy that mimics the process of fetal development of articular cartilage by successive-sustained release of zone-specific morphogens (BMP7, IGF1, IHH) within a fetal-based matrix. The successive release of zone-specific morphogens sequentially differentiates the encapsulated Mesenchymal stem cells (MSCs) to pre-chondrocytes, pre-hypertrophic, and hypertrophic chondrocytes, leading to successive generation of zonal structure of articular cartilage. The approach consists of a) generating microcapsules for delayed-sustained release of zone-specific morphogens, b) synthesizing a crosslinkable matrix based on fetal cartilage, mixing chondroprogenitor cells and cells in the crosslinkable precursor solution, and crosslink to form an injectable monolayer or a multilayer implant for the regeneration of articular cartilage.
Potential Applications:
The development of therapies with the ability to regenerate the zonal organization present in articular cartilage, with a view to preventing permanent disability in patients suffering from post-traumatic osteoarthritis (PTOA).
Advantages and Benefits:
1. The cell/morphogen-loaded in situ crosslinkable composition is fetal-mimetic. As fetal articular cartilage injuries heal spontaneously without forming fibrous tissue, the composition regenerates the zonal organization of articular cartilage thus avoiding fibrocartilage formation. Existing products are not designed with the idea of mimicking the fetal generation of articular cartilage.
2. The matrix for the delivery of cells and mophogens is produced from fetal bovine articular cartilage. The fetal nature of the matrix can promote a fetal-mimetic regeneration that avoids fibrocartilage formation.
3. Zone-specific morphogenesis are released sequentially in situ to guide the formation of zonal structure of articular cartilage.
4. The cell/morphogen-loaded composition can be injected to the defect site compatible with minimally invasive procedures or it can be pre-formed as a multilayer and inserted in the defect site as an implant.